Positron emission tomography's (PET'S) unique in vivo molecular imaging ability can be deployed to enhance research on gene expression/therapy for cancer and drug development research, and it improves clinical diagnosis by localizing small tumors in human, thus improving the accuracy of staging and treatment planning. The long-term objective of our project is to lower the cost and improve the imaging performance of PET. The detection system of a PET camera dictates its image quality and cost. Continued development of our high resolution, lower cost PET detector design concept and high-speed electronics is proposed. In the last funding period, an inexpensive high-resolution PET detector concept (PQS) was proposed and studied. In that study, the PQS detector concept was demonstrated to be technically and practically achievable using traditional BGO scintillation detectors. We propose to further develop the PQS approach with the newer and faster scintillation crystals of LSO and GSO, which can further improve PET resolution significantly and cost-effectively. The specific aims of the project are: (1) To study the application of LSO and GSO to the PQS design. The much higher light output of LSO/GSO could well lead to ultrahigh PET resolution of 1-2 mm for human and mouse applications. Prototype LSO-PQS and GSO-PQS detectors will be developed, (2) To study and develop a new, highly efficient detector-production method that can lower the costly detector-production labor of ultrahigh resolution PET by 90%. This method reduces the processing of 160,000 small detectors to 1000 much larger units, (3) To develop a fast automatic PET detector-tuning method that can equalize the amplifications of all the photomultipliers (1 000) in a PET in less than 5 minutes instead of 1-4 hrs, so that a PET can be tuned during patient loading to maximize PET imaging performance before scanning a patient. This method shuns the conventional external radiation sources, (4) To develop a practical method of (a) measuring the depth-of-interaction for each detected gamma ray in a PQS detection system and (b) doubling the spatial-data sampling without mechanical motion. It utilizes a 2-layer offset detector design to further improve the image resolution of a PET, (5 ) To adapt the high-speed-pileup-prevention electronics developed in the last period to the fast LSO/GSO PQS detectors to further enhance the high radiation level imaging capability of these detectors. This electronics can eliminate image artifacts due to detector signal-pileups and shorten patient scan time.